a study of rucaparib administered with radiation in patients with triple negative breast cancer with an incomplete response following chemotherapy

Conditions: Breast Cancer

Summary: the purpose of this study is to test the safety of a study drug called rucaparib, administered in combination with the type of radiation therapy that is usually given to women with your form of breast cancer.


Eligibility criteria:
inclusion criteria: * female, ≥ 18 years of age. * non-metastatic, histologically or cytologically-confirmed tnbc (defined as er \<1%, pr \<1%, her-2-neu 0-1+ by ihc or fish-negative or as per md discretion), with evidence of residual disease in the breast or lymph nodes after neoadjuvant chemotherapy, at the time of definitive surgical treatment. * non-metastatic, histologically or cytologically-confirmed hormone-receptor positive, her2/neu negative breast cancer (defined as er \>1% or pr \>1% and her-2/neu 0-1+ by ihc or fish-negative, or as per md discretion), with evidence of residual grade 3 invasive breast cancer and either 1) \>5 cm of residual disease in the breast or 2) ≥ 4 axillary lns in the axilla after neoadjuvant chemotherapy, at the time of definitive surgical treatment. * definitive surgical treatment with breast-conserving surgery or mastectomy and axillary lymph node evaluation. * at least 6-month life expectancy, ecog performance status \< 2. * willingness to discontinue any cytotoxic chemotherapeutic agents, and biologic therapy at least 2 weeks prior to the start of rt. * adequate organ function (assessed within 30 days prior to initiation of protocol treatment, unless otherwise indicated) as follows: hematology * absolute neutrophil count (anc) ≥1500/mm\^3 * platelet count ≥100,000/mm\^3 * hemoglobin ≥9.0 g/dl (after transfusion if required) renal function * creatinine serum ≤ 1.5 mg/dl or creatinine clearance ≥ 45 ml/min\^a hepatic function * bilirubin ≤ 1.5 mg/dl * aspartate aminotransferase (ast) ≤ 2.5 x uln\^b * alanine aminotransferase (alt) ≤ 2.5 x uln uln = upper normal limit of institution's normal range 1. if calculated creatinine clearance is \< 45ml/min, a 24-hour urine collection for creatinine clearance may be performed 2. subjects with documented gilbert's disease may have bilirubin up to 2.5 mg/dl * negative serum pregnancy test within 14 days prior to study treatment if a woman has child-bearing potential. subjects of child bearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. * ability to swallow and retain oral medications. * written informed consent obtained from subject and ability for subject to comply with the requirements of the study. * female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the duration of study participation. should a woman become pregnant while participating on study, she should inform the treating physician immediately. exclusion criteria: * gross residual tumor on imaging or positive margins after breast conserving surgery that are un-excised, as radiation dose in the study will be limited to 60 gy. * complete pathologic response to nac. * receipt of parp inhibitor prior to rt. * pregnant or expecting to conceive within the projected duration of the trial, starting with screening visit through 180 days after the last dose of trial treatment. * prior history of radiation therapy to the ipsilateral breast and/or regional nodes is not allowed (prior rt to other sites is permitted). * patients with breast augmentation implants are excluded. * history of allergic reactions attributed to compounds of similar chemical or biologic composition to rucaparib. * concomitant anti-neoplastic treatment is not allowed during protocol treatment and should be completed at least 2 weeks prior to commencement of protocol treatment, with resolution of associated acute toxicities. bisphosphonates are permitted without restriction even during protocol treatment. maintenance pembrolizumab is permitted during the protocol treatment. * significant comorbidity: patients with clinically significant and uncontrolled major disease or disorder that could exacerbate potential toxicities, confound safety assessments, require excluded therapy for management, or limit study compliance. * ongoing therapy with other investigational agents. patients may not be receiving any other investigational agents. * unresolved toxicity from other agents. patients with unresolved ctcae v4.03 grade 3 or greater toxicity from prior administration of another investigational drug and/or anti-cancer treatment are not eligible.

Keywords: rucaparib radiotherapy triple negative breast cancer 18-002